Biochemistry of glucose and insulin

Question 1

What is the molecular structure of insulin?

Answer 1

A peptide hormone released by beta cells which makes up 60-80% of islets of langerhan’s

Calcium-dependent endopeptidases cleave C-peptides from proinsulin to form insulin (A and B chains connected by sulfide bridges)

Some minor amino acid sequence changes could lead to different turnover rates of insulin in blood - allowing for different insulin preparations

Question 2

What molecular mechanisms lead to insulin secretion upon increased glucose?

Answer 2

1. Glucose enters b cells through the GLUT2 glucose transporter down its concentration gradient and is phosphorylated by glucokinase
2. Glucokinase’s Km for glucose lies in the physiological range of concentrations (This Km dictates physiological level of glucose)
   *A change of glucose concentration leads to a dramatic change in glucokinase activity
3. Increased metabolism of glucose leads to an increase in intracellular ATP concentration
4. ATP inhibits the ATP-sensitive K+ channel KATP
5. Inhibition of KATP leads to depolarisation of the cell membrane
6. Depolarisation of the cell membrane results in opening of voltage-gated Ca2+ channels
7. An increase in internal Ca2+ concentration leads to fusion of secretory vesicles with the cell membrane and release of insulin

Question 3

What is the level of glucokinase activity in Type 2 DM, and how would this affect beta cells?

Question 4

Describe insulin signalling

Question 5

What conditions would arise from defective insulin
secretion?

Answer 5

Hypoglycaemic coma
1. Type 1 Diabetes Mellitus = autoimmune destruction of the pancreatic beta cells
*Dx = evidence of the presence of specific autoantibodies + declining C-peptide production

2. T2DM

Question 6

What conditions would arise from defective insulin
signalling?

Question 7

What are the implication of ketone body formation and treatment in diabetes?

Question 8

What is diabetic ketoacidosis (DKA) and how does it present?